This proposal focuses on development of technology that is suited for both ultra-high resolution animal imaging systems and other applications such as human breast and head imaging. An integral part of our work to date is the development of a highly modular approach to the detectors and supporting electronics. This approach assures that imaging resources built using the technology can easily adapt to the changing demands of the biological research. In the previous funding period we made considerable progress in developing new approaches for single-ended readout depth-of-interaction detectors. This effort included premising preliminary data using sub-surface laser engraving techniques to control the light sharing between shared crystals. The wealth of information from the detectors present a challenge in data collection electronics and to help solve that challenge we developed a new application specific integrated circuit (ASIC) with row/column and row/column/ summing to reduce the amount of required data to be collected without losing any of the basic detector data. In this renewal application, we propose to further develop detector modules, electronics, and FPGA firmware to support a depth-of-interaction (DOI) detector designs and supporting electronics. A major focus is on cost effective designs, and therefore our effort will focus on bot the SSLE work already started and a new generation of ASICs to eliminate all but power cables to the detectors (reducing cost, making system integration much simpler, and improving reliability) using advanced RF communication techniques. The overall goal is to achieve spatial resolutions < 1.0 mm with sensitivity in a typical small animal configuration of > 15%. The effort will include the development of maximum likelihood estimators for crystal-of-interaction and depth-of-interaction in both or discrete crystal and monolithic crystal detector designs at the detector level. The net result of our work will be contributions to the general knowledge of options for detector and electronics design for high-resolution detector systems as well as insight into methods to control light response functions in crystals using SSLE. The new ASIC will offer a wide variety of options for new systems by getting rid of the essentially all cables ad connectors between the detectors and supporting electronics. This work is developing for new scanner designs to address biological research and clinical needs.